Although a great deal is known about the signaling events that promote nuclear translocation of NF-κB, how cellular biophysics and the microenvironment might regulate the dynamics of this pathway is poorly understood. In this study, we used high-content image analysis and Bayesian network modeling to ask whether cell shape and context features influence NF-κB activation using the inherent variability present in unperturbed populations of breast tumor and non-tumor cell lines. Cell–cell contact, cell and nuclear area, and protrusiveness all contributed to variability in NF-κB localization in the absence and presence of TNFα. Higher levels of nuclear NF-κB were associated with mesenchymal-like versus epithelial-like morphologies, and RhoA-ROCK-myosin II signaling was critical for mediating shape-based differences in NF-κB localization and oscillations. Thus, mechanical factors such as cell shape and the microenvironment can influence NF-κB signaling and may in part explain how different phenotypic outcomes can arise from the same chemical cues.

中文翻译：

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细胞形状和微环境调节乳腺上皮细胞和肿瘤细胞中 NF-κB 的核转位。

尽管人们对促进 NF-κB 核转位的信号事件有很多了解，但对细胞生物物理学和微环境如何调节该途径的动力学知之甚少。在这项研究中，我们使用高内涵图像分析和贝叶斯网络建模来利用未受干扰的乳腺肿瘤和非肿瘤细胞系群中存在的固有变异性来询问细胞形状和上下文特征是否影响 NF-κB 激活。细胞 - 细胞接触、细胞和核区域以及突出都有助于在 TNFα 不存在和存在的情况下 NF-κB 定位的变异性。较高水平的核 NF-κB 与间充质样和上皮样形态有关，RhoA-ROCK-肌球蛋白 II 信号传导对于介导 NF-κB 定位和振荡中基于形状的差异至关重要。因此，细胞形状和微环境等机械因素会影响 NF-κB 信号传导，并可能部分解释相同的化学信号如何产生不同的表型结果。